Department of Urology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Prostate Cancer Prostatic Dis. 2012 Sep;15(3):250-5. doi: 10.1038/pcan.2012.9. Epub 2012 Mar 27.
The influence of the bisphosphonate zoledronic acid (ZA) on prostate cancer (PC) growth, adhesion and invasive behavior was investigated.
PC-3, DU-145 and LNCaP cells were treated with ZA, and tumor-cell growth was then investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, tumor-cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins, as well as migratory properties of the cells, was evaluated. Integrin β subtypes, integrin-dependent signaling, as well as cell-cycle regulating proteins, were analyzed by western blots.
ZA dose-dependently reduced tumor-cell growth but did not impair tumor-endothelium and tumor-matrix interaction. However, ZA significantly inhibited tumor migration and invasive activity. Cyclin E was reduced by ZA in LNCaP and DU-145, and p21 was elevated in LNCaP cells. p27 was upregulated in all tumor cell lines, compared with the controls. ZA elevated β1-integrin in PC-3 and diminished β4-integrin in PC-3 and DU-145 cells.
ZA inhibits PC growth and motility but does not influence the mechanical contact between tumor cells and the vascular wall.
研究了双膦酸盐唑来膦酸（ZA）对前列腺癌（PC）生长、黏附和侵袭行为的影响。
用 ZA 处理 PC-3、DU-145 和 LNCaP 细胞，然后通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法研究肿瘤细胞的生长情况。此外，还评估了肿瘤细胞与血管内皮或固定细胞外基质蛋白的黏附能力以及细胞的迁移特性。通过 Western blot 分析整合素 β 亚基、整合素依赖性信号以及细胞周期调节蛋白。
ZA 呈剂量依赖性地降低肿瘤细胞生长，但不损害肿瘤-内皮和肿瘤-基质相互作用。然而，ZA 显著抑制肿瘤迁移和侵袭活性。ZA 在 LNCaP 和 DU-145 中降低了细胞周期蛋白 E，在 LNCaP 细胞中升高了 p21。与对照组相比，所有肿瘤细胞系中的 p27 均上调。ZA 在 PC-3 中上调了β1 整合素，在 PC-3 和 DU-145 细胞中降低了β4 整合素。
ZA 抑制 PC 的生长和迁移，但不影响肿瘤细胞与血管壁之间的机械接触。
